We have developed a novel method to augment current cell replacement therapies for Parkinson's Disease and seek support to optimize this technique. In preliminary experiments, we show that the introduction of a single gene into neural precursor cells can specifically and significantly increase the proportion of those cells that adopt a dopaminergic phenotype. Furthermore, this gene induces a dopaminergic phenotype even in precursor cells that derive from brain regions which do not normally generate dopaminergic neurons. We seek to develop viral vectors to improve gene delivery to neural precursor cells so that we may increase further the proportion of these cells that become dopaminergic. In addition, we propose to transplant these cells into a rat lesion model of Parkinson's Disease to determine, in acute experiments, whether they survive and retain their dopaminergic phenotype once transplanted. Finally, we propose to characterize more completely the properties of these cells through immunocytochemical and molecular analysis. Through this program of experimentation we seek to prepare for preclinical and ultimately clinical trials of the ability of this genetic enhancement of neural precursor cells to improve significantly current cell replacement therapies for Parkinson's Disease. PROPOSED COMMERCIAL APPLICATIONS: The program of research and product development described in this application has the potential to enhance significantly the efficacy of transplantation therapies for Parkinson's Disease.